During the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition a study was presented about a phase III trial for treating myeloma. This treatment supports the current three-drug standard of care with a fourth drug, a monoclonal antibody that is designed to fight cancer while also stimulating the immune system.
According to results from the first primary endpoint of the phase III trial, the patients that have been newly diagnosed with myeloma and are receiving the anti-CD38 monoclonal antibody isatuximab in addition to the 3-component induction therapy lenalidomide, bortezomib, and dexamethasone (RVd) were significantly more likely to reach Minimal Residual Disease (MRD) negativity (no evidence of cancer in the bone marrow) compared to those patients receiving RVd alone.
50.1 % of the study participants who obtained isatuximab-RVd versus 35.6 % of those receiving RVd only reach MRD negativity in the bone marrow after their induction treatment.
“This is the first phase III trial to successfully challenge a standard of care that is broadly used in the U.S. and Europe,” said Prof. Hartmut Goldschmidt, MD, of the Heidelberg University Hospital (UKHD) and National Center of Tumor Diseases Heidelberg (NCT) in Germany. “Our results support this treatment as a new standard of care in transplant-eligible patients with newly diagnosed myeloma.”
Treatment for myeloma is most common in people over the age of 60, has advanced substantially in recent years, achieving a 10-year survival rate of up to 70 %. By adding isatuximab to RVd, the researchers worked to increase survival rates and completely eradicate the cancer in the bone marrow for more patients. Isatuximab is approved in the U.S., Europe, and other countries for myeloma patients who have already undergone previous rounds of treatment. This new trial assessed its use as part of the first-line treatment for newly diagnosed, transplant-eligible patients up to 70 years of age.
“Isatuximab acts in two ways – one is the direct effect of the antibody on myeloma cells, and the other is the immunostimulatory effect,” said Dr. Goldschmidt. “The idea is that if the immune system is stimulated by isatuximab, treatment of myeloma will be more effective.”
The trial had 662 newly diagnosed patients enrolled at 67 medical centers throughout Germany. Half of the patients received induction therapy isatuximab plus RVd and the other half received RVd alone. The duration of induction therapy was 18 weeks for both treatment arms. In addition to meeting the trial’s primary endpoint for minimal residual disease negativity in the bone marrow, those patients that received isatuximab were notably more likely to achieve a complete response or a very good partial response and less likely to show evidence of disease progression. The researchers also found no differences among subgroups, suggesting all patients benefit from the addition of isatuximab to RVd. There was no major difference between groups in terms of overall adverse events or serious adverse events. The most common adverse events in both groups were blood and lymphatic system disorders, infections, and nervous system disorders, with low white blood cell, counts being more frequent in the isatuximab-RVd group.
The trial is ongoing and will next evaluate the impact of isatuximab-RVd versus RVd induction therapy after autologous stem cell transplantation, as well as the drug’s potential effects when used as part of the maintenance regimen with lenalidomide.